RT Journal Article
SR Electronic
T1 T cell receptor repertoire signatures associated with COVID-19 severity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.30.470640
DO 10.1101/2021.11.30.470640
A1 Jonathan J. Park
A1 Kyoung A V. Lee
A1 Stanley Z. Lam
A1 Sidi Chen
YR 2021
UL http://biorxiv.org/content/early/2021/12/02/2021.11.30.470640.abstract
AB T cell receptor (TCR) repertoires are critical for antiviral immunity. Determining the TCR repertoires composition, diversity, and dynamics and how they change during viral infection can inform the molecular specificity of viral infection such as SARS-CoV-2. To determine signatures associated with COVID-19 disease severity, here we performed a large-scale analysis of over 4.7 billion sequences across 2,130 TCR repertoires from COVID-19 patients and healthy donors. TCR repertoire analyses from these data identified and characterized convergent COVID-19 associated CDR3 gene usages, specificity groups, and sequence patterns. T cell clonal expansion was found to be associated with upregulation of T cell effector function, TCR signaling, NF-kB signaling, and Interferon-gamma signaling pathways. Machine learning approaches accurately predicted disease severity for patients based on TCR sequence features, with certain high-power models reaching near-perfect AUROC scores across various predictor permutations. These analyses provided an integrative, systems immunology view of T cell adaptive immune responses to COVID-19.Competing Interest StatementThe authors have declared no competing interest.